MITF 对细胞周期和增殖相关基因的调控
中文名称
通路描述
MITF 的活性水平决定了其是促增殖还是抗增殖作用。在被称为 MITF 作用机制的调光器模型中，低水平的 MITF 活性与去分化、侵袭、p27kip (CDKN1B) 介导的细胞周期阻滞和低增殖率相关，而高水平的 MITF 通过上调细胞周期和有丝分裂基因（如 CDK2、CCNB1、CCND1、MET、PLK1、CENPA 和 NDC80）来驱动增殖。在更高水平的 MITF 下，细胞周期通过表达 p21 (CDKN1A) 和 p16 (CDKN2A) 而被阻滞。MITF 活性和靶基因表达的这种调光器模型也可用于描述 MITF 在黑色素瘤发展中的作用，不同靶基因组的激活驱动增殖和侵袭，而不激活色素生成基因。
英文描述
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation Depending on the overall level of activity, MITF may have a proliferative or antiproliferative role. In what has been termed a rheostat model of action, low-levels of MITF activity are associated with dedifferentiation, invasion, p27kip (CDKN1B)-dependent cell cycle arrest and low proliferative rates, while higher MITF activity drive proliferation by upregulation of cell-cycle and mitotic genes such as CDK2, CCNB1, CCND1, MET, PLK1, CENPA and NDC80 (Carreira et al, 2006; Strub et al, 2011; McGill et al, 2006; Beuret et al, 2007; Webster et al, 2014). At even higher MITF levels, cell-cycle is arrested by virtue of expression of p21 (CDKN1A) and p16 (CDKN2A) (Carreira et al, 2005; Loercher et al, 2005; reviewed in Goding and Arnheiter, 2019). This rheostat model of MITF activity and target gene expression can also be used to describe the role of MITF in the development of melanoma, with activation of different groups of target genes driving proliferation and invasion without activation of pigmentation genes (Hoek and Goding, 2010; reviewed in Mort et al, 2015; White and Zon, 2008).
所含基因
17 个基因